Immediate postoperative care on high dependency unit or ward following microvascular free tissue transfer: lessons learnt from a change in practice imposed during the COVID-19 pandemic.

The COVID-19 pandemic resulted in sudden changes to the established practice of using the high dependency unit (HDU) for the first night of postoperative care following microvascular free tissue transfer. Patients were managed instead on the head and neck ward. This retrospective case-note review aimed to report outcomes in consecutive patients treated before and during the pandemic, and to reflect on the implications of ward-based rather than HDU care. A total of 235 patients had free tissue transfer between 3 January 2019 and 25 February 2021: 125 before (lockdown 23 March 2020), and 110 during the pandemic (52 ward-managed and 58 HDU-managed). There were subtle case-mix differences during the pandemic, with 92% of ward-treated patients having oral cancers compared with 64% of HDU patients, and 73% of ward patients having a tracheostomy compared with 40% of HDU patients. Ward patients were less likely to receive electrolyte replacement (45% HDU vs 0% ward) and inotropes (12% HDU vs 2% ward). There were fewer returns to theatre for evacuation of a haematoma or re-anastomosis during the pandemic than there were before it. Other than fewer haematoma complications during the pandemic, the nature of complications was similar. In conclusion, the dramatic changes imposed by the pandemic have shown that the ward is a safe place for patients to be cared for immediately postoperatively, and it alleviates the bed pressures experienced in HDU. Careful case selection and clear criteria are required to identify patients who need the HDU.

Microvascular anastomotic coupler devices versus hand-sewn technique for arterial anastomosis: a systematic review.

The use of microvascular anastomotic coupling devices (MACD) is an established technique for venous anastomosis. However, literature on arterial MACD is conflicting. We report, to our knowledge, the first registered systematic review of its kind to evaluate the safety and efficiency of arterial MACD in free flaps. We performed a PRISMA-guided systematic review (PROSPERO-registered) and identified reports using a search algorithm in MEDLINE/EMBASE. The rate of arterial thrombosis was set as the primary outcome. Secondary outcomes included flap survival, failure rates, and comparison of MACD and the conventional hand-sewn technique. From the 17 studies identified, 2672 free flap reconstructions were performed and 640 arterial anastomoses with MACD attempted (622 completed, 97.2%). The pooled incidence of arterial thrombosis was 2.1% (13/622), and overall flap failure rate 4.34% (116/2672). The total number of arterial MACD procedures performed first time, with no perioperative complications, revisions, or thrombosis, was 88.9% (569/640). Grading of Recommendations, Assessment, Development and Evaluation (GRADE) quality analysis revealed low quality and significant heterogeneity. The use of arterial MACD is a safe and efficient alternative to hand-sewn anastomosis, with more recent literature showing excellent results. However, further evaluation is required with controlled trials.

Use of the subclavian vessels for microvascular reconstruction in the vessel-depleted neck.

The previously treated neck is a serious problem if further free tissue transfer reconstruction is required. Vessel depletion is often a terrifying finding that creates the need for novel approaches to access vessels that lie outside the anatomical region of the head and neck. We present what is, to our knowledge, the first case of utilising the subclavian artery and vein in head and neck reconstruction. We describe the anatomical details and a step-by-step access approach, together with tips on how to perform safe and effective microvascular anastomoses. The quality of the subclavian vessels is excellent, and access to the area is straightforward provided it is carefully planned. The technique could be considered more often in the vessel-depleted neck.

Adjuvant management of locally advanced oral squamous cell carcinoma - real-world challenges and opportunities.

Patients with locally advanced oral squamous cell cancer (LAOSCC) are treated with adjuvant radiotherapy (RT) or chemoradiotherapy (CRT) following surgical ablation. This depends on the pathological risk factors and aims to reduce the risk of local recurrence and improve survival. Delivery of these aggressive treatments is, however, challenging particularly following major surgery. To inform the adaptations necessary to deliver gold-standard therapy, we aimed to describe real-world delivery of multimodality treatment in LAOSCC, in a UK population with high levels of disease incidence and low socioeconomic status. Patients with LAOSCC (T1-4 N1-3/T3-4 N0) who were treated between October 2014 and October 2016 and had a minimum follow up of 24 months were included. They were identified using the Somerset Cancer Register and data were collected through retrospective case note review. Approval was obtained from the audit departments at the relevant NHS institutions, and data were analysed using IBM SPSS Statistics for Windows version 24 (IBM Corp). The analysis included 129 patients with 82% having an initial performance status (PS) of 0-1. The most frequent change in PS was a one point drop (46%). Twenty of the 93 eligible patients (22%) underwent adjuvant CRT. A total of 37 (40%) began adjuvant CRT/RT within 42 days, and 79 (85%) within 56 days. A delay in initiating adjuvant therapy was associated with higher rates of complications and a longer postoperative hospital stay. Concordance between imaging and pathological nodal staging was poor (cK 0.223). PS frequently declines after complex surgical procedures and long postoperative recovery periods, leading to difficulties providing adjuvant treatments within the national guidance of 42 days. Frequent deviation from planned adjuvant therapies highlights the need for improved treatment strategies.

Enhanced Carbapenemase Producing Enterobacterales (CPE) Screening in a Paediatric Population.

Aims The aim of this period of extended screening (to include those being readmitted to TSCUH if they had been an inpatient in the preceding year) was to determine whether any additional CPE positive patients were identified. Methods Education was given to Clinical Nurse Managers regarding those requiring screening and reinforced at daily handover meetings. Results 917 patients were screened during the four-month period; only two positive patients were identified, who would have been screened under the previous local guidelines. Conclusion The screening of an additional 314 patients (34% increase compared with the same period in the previous year) yielded no positive results, showing that patients whose only risk factor was admission to TSCUH within the previous year do not currently require screening.

Diagnostic Value of Brain Calcifications in Adult-Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia.

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia is a rare neurodegenerative disease resulting from mutations in the colony stimulating factor 1 receptor gene. Accurate diagnosis can be difficult because the associated clinical and MR imaging findings are nonspecific. We present 9 cases with intracranial calcifications distributed in 2 brain regions: the frontal white matter adjacent to the anterior horns of the lateral ventricles and the parietal subcortical white matter. Thin-section (1-mm) CT scans are particularly helpful in detection due to the small size of the calcifications. These calcifications had a symmetric "stepping stone appearance" in the frontal pericallosal regions, which was clearly visible on reconstructed sagittal CT images. Intrafamilial variability was seen in 2 of the families, and calcifications were seen at birth in a single individual. These characteristic calcification patterns may assist in making a correct diagnosis and may contribute to understanding of the pathogenesis of leukoencephalopathy.

Spontaneous coronary artery dissection in a parturient with Nail-Patella syndrome.

Spontaneous coronary artery dissection is an uncommon cause of acute coronary syndrome, occurring predominantly in women during and immediately after pregnancy; it carries a mortality rate of greater than 50%. While the exact etiology is unknown, possible contributing factors include pregnancy-related hormonal, connective tissue and hemodynamic changes. We present a case of a 35-year-old multigravid woman with Nail-Patella syndrome who developed an acute myocardial infarction secondary to spontaneous coronary artery dissection during labor which was not diagnosed until after delivery. We hypothesize that abnormal collagen fiber formation found in Nail-Patella syndrome may have put her at an increased risk of coronary dissection and myocardial infarction. Regardless of etiology, a delay in diagnosis of myocardial ischemia can lead to significant morbidity and mortality. In light of the increasing burden of cardiac disease in the obstetric population, clinicians should remain vigilant for signs of myocardial infarction and prepare for definitive diagnosis and treatment.

Stretched to the limit; can a short pelagic larval duration connect adult populations of an Indo-Pacific diadromous fish (Kuhlia rupestris)?

Freshwater species on tropical islands face localized extinction and the loss of genetic diversity. Their habitats can be ephemeral due to variability in freshwater run-off and erosion. Even worse, anthropogenic effects on these ecosystems are intense. Most of these species are amphidromous or catadromous (i.e. their life cycle includes a marine larval phase), which buffers them against many of these effects. A long pelagic larval duration (PLD) was thought to be critical to ensure the colonization and persistence in tropical islands, but recent findings indicated that several species with short PLDs are successful in those ecosystems. To test the potential of a short PLD in maintaining genetic connectivity and forestalling extirpation, we studied Kuhlia rupestris, a catadromous fish species with an extensive distribution in the western Pacific and Indian Oceans. Using a combination of molecular genetic markers (13 microsatellite loci and two gene regions from mtDNA) and modelling of larval dispersal, we show that a short PLD constrains genetic connectivity over a wide geographical range. Molecular markers showed that the short PLD did not prevent genetic divergence through evolutionary time and speciation has occurred or is occurring. Modelling of larvae dispersal suggested limited recent connectivity between genetically homogeneous populations across the Coral Sea. However, a short PLD can maintain connectivity on a subocean basin scale. Conservation and management of tropical diadromous species needs to take into account that population connectivity may be more limited than previously suspected in those species.

A review of the application of molecular genetics for fisheries management and conservation of sharks and rays.

Since the first investigation 25 years ago, the application of genetic tools to address ecological and evolutionary questions in elasmobranch studies has greatly expanded. Major developments in genetic theory as well as in the availability, cost effectiveness and resolution of genetic markers were instrumental for particularly rapid progress over the last 10 years. Genetic studies of elasmobranchs are of direct importance and have application to fisheries management and conservation issues such as the definition of management units and identification of species from fins. In the future, increased application of the most recent and emerging technologies will enable accelerated genetic data production and the development of new markers at reduced costs, paving the way for a paradigm shift from gene to genome-scale research, and more focus on adaptive rather than just neutral variation. Current literature is reviewed in six fields of elasmobranch molecular genetics relevant to fisheries and conservation management (species identification, phylogeography, philopatry, genetic effective population size, molecular evolutionary rate and emerging methods). Where possible, examples from the Indo-Pacific region, which has been underrepresented in previous reviews, are emphasized within a global perspective.

Genetic population structure of grey mackerel Scomberomorus semifasciatus in northern Australia.

This study used mtDNA sequence and microsatellite markers to elucidate the population structure of Scomberomorus semifasciatus collected from 12 widespread sampling locations in Australia. Samples (n = 544) were genotyped with nine microsatellite loci, and 353 were sequenced for the control (384 bp) and ATPase (800 bp) mtDNA gene regions. Combined interpretation of microsatellite and mtDNA data identified four genetic stocks of S. semifasciatus: Western Australia, north-west coast of the Northern Territory, Gulf of Carpentaria and the eastern coast of Queensland. Connectivity among stocks across northern Australia from the Northern Territory to the eastern coast of Queensland was high (mean F(ST) = 0·003 for the microsatellite data and Φ(ST) = 0·033 and 0·009 for control region and ATPase, respectively) leading to some uncertainty about stock boundaries. In contrast, there was a clear genetic break between the stock in Western Australia compared to the rest of northern Australia (mean F(ST) = 0·132 for the microsatellite data and Φ(ST) = 0·135 and 0·188 for control region and ATPase, respectively). This indicates a restriction to gene flow possibly associated with suboptimal habitat along the Kimberley coast (north Western Australia). The appropriate scale of management for this species corresponds to the jurisdictions of the three Australian states, except that authorities in Queensland and Northern Territory should co-ordinate the management of the Gulf of Carpentaria stock.

IUCN classification zones concord with, but underestimate, the population genetic structure of the zebra shark Stegostoma fasciatum in the Indo-West Pacific.

The Indo-West Pacific (IWP), from South Africa in the western Indian Ocean to the western Pacific Ocean, contains some of the most biologically diverse marine habitats on earth, including the greatest biodiversity of chondrichthyan fishes. The region encompasses various densities of human habitation leading to contrasts in the levels of exploitation experienced by chondrichthyans, which are targeted for local consumption and export. The demersal chondrichthyan, the zebra shark, Stegostoma fasciatum, is endemic to the IWP and has two current regional International Union for the Conservation of Nature (IUCN) Red List classifications that reflect differing levels of exploitation: 'Least Concern' and 'Vulnerable'. In this study, we employed mitochondrial ND4 sequence data and 13 microsatellite loci to investigate the population genetic structure of 180 zebra sharks from 13 locations throughout the IWP to test the concordance of IUCN zones with demographic units that have conservation value. Mitochondrial and microsatellite data sets from samples collected throughout northern Australia and Southeast Asia concord with the regional IUCN classifications. However, we found evidence of genetic subdivision within these regions, including subdivision between locations connected by habitat suitable for migration. Furthermore, parametric F(ST) analyses and Bayesian clustering analyses indicated that the primary genetic break within the IWP is not represented by the IUCN classifications but rather is congruent with the Indonesian throughflow current. Our findings indicate that recruitment to areas of high exploitation from nearby healthy populations in zebra sharks is likely to be minimal, and that severe localized depletions are predicted to occur in zebra shark populations throughout the IWP region.

Insights into the dynamics of hereditary diffuse leukoencephalopathy with axonal spheroids.

OBJECTIVE: To report a new American family with hereditary diffuse leukoencephalopathy with spheroids (HDLS), including serial, presymptomatic and symptomatic, cranial MRIs from the proband. METHODS: We report clinical and genealogic investigations of an HDLS family, sequential brain MRIs of the proband, and autopsy slides of brain tissue from the proband's father. RESULTS: We identified seven affected family members (five deceased). The mean age at symptomatic disease onset was 35 years (range: 20-57), and the mean disease duration was 16 years (range: 3-46). Five affected individuals initially manifested memory disturbance and behavioral changes, whereas two experienced a mood disorder as their presenting symptom. Our proband's father had been diagnosed clinically with vascular dementia, but his brain autopsy was consistent with HDLS. The proband had a cranial MRI prior to symptom onset, with two subsequent MRIs performed during follow-up. These serial images reveal a progressive, confluent, frontal-predominant leukoencephalopathy with symmetric cortical atrophy. CONCLUSIONS: The proband of our newly identified hereditary diffuse leukoencephalopathy with spheroids (HDLS) kindred had subtle evidence of an incipient leukoencephalopathy on a presymptomatic cranial MRI. Conceivably, MRI may facilitate identifying affected presymptomatic individuals within known HDLS kindreds, increasing the likelihood of isolating the causative genes.

A PCR assay for gender assignment in dugong (Dugong dugon) and West Indian manatee (Trichechus manatus).

Gender assignment for some aquatic mammals in the field is difficult. Molecular sexing from tissue biopsies is possible as males are heterogametic. Here we describe a multiplex PCR assay that amplifies the male specific SRY gene and differentiates ZFX and ZFY gametologues in two sirenian species, dugong (Dugong dugon) and West Indian manatee (Trichechus manatus). The assay was validated with animals of known gender and proved accurate and robust to experimental failure.

Phylogeography of the green turtle, Chelonia mydas, in the Southwest Indian Ocean.

Patterns of mitochondrial DNA (mtDNA) variation were used to analyse the population genetic structure of southwestern Indian Ocean green turtle (Chelonia mydas) populations. Analysis of sequence variation over 396 bp of the mtDNA control region revealed seven haplotypes among 288 individuals from 10 nesting sites in the Southwest Indian Ocean. This is the first time that Atlantic Ocean haplotypes have been recorded among any Indo-Pacific nesting populations. Previous studies indicated that the Cape of Good Hope was a major biogeographical barrier between the Atlantic and Indian Oceans because evidence for gene flow in the last 1.5 million years has yet to emerge. This study, by sampling localities adjacent to this barrier, demonstrates that recent gene flow has occurred from the Atlantic Ocean into the Indian Ocean via the Cape of Good Hope. We also found compelling genetic evidence that green turtles nesting at the rookeries of the South Mozambique Channel (SMC) and those nesting in the North Mozambique Channel (NMC) belong to separate genetic stocks. Furthermore, the SMC could be subdivided in two different genetic stocks, one in Europa and the other one in Juan de Nova. We suggest that this particular genetic pattern along the Mozambique Channel is attributable to a recent colonization from the Atlantic Ocean and is maintained by oceanic conditions in the northern and southern Mozambique Channel that influence early stages in the green turtle life cycle.

Autosomal dominant dystonia-plus with cerebral calcifications.

OBJECTIVE: To report genealogic, clinical, imaging, neuropathologic, and genetic data from a Canadian kindred with dystonia and brain calcinosis originally described in 1985. METHODS: The authors performed clinical examinations and CT and PET studies of the head and analyzed blood samples. One autopsy was performed. RESULTS: The family tree was expanded to 166 individuals. No individuals were newly affected with dystonia, but postural tremor developed in two. The mean age at symptom onset was 19 years. Eight individuals had dystonia: three focal, one segmental, one multifocal, and three generalized. Seven displayed additional signs: chorea, intellectual decline, postural tremor, and dysarthria. CT studies were performed on five affected and 10 at-risk family members. All affected individuals and eight at-risk individuals had brain calcinosis. PET scans in two individuals showed reduced D(1)- and D(2)-receptor binding and reduced uptake of 6-[(18)F]fluoro-l-dopa. Autopsy of one affected individual showed extensive depositions of calcium in the basal ganglia, thalamus, cerebral white matter, and cerebellum. No specific immunohistochemistry abnormalities were seen. Genome search data showed no evidence of linkage to the previously described loci IBGC1, DYT1, and DYT12. CONCLUSIONS: The phenotype of this family consists of dystonia-plus syndrome. Brain calcium deposits vary in severity and distribution, suggesting that calcifications alone are not entirely responsible for the observed clinical signs. Further studies are needed to elucidate the etiology of this heterogeneous group of disorders.

Routine use of gradient-echo MRI to screen for cerebral amyloid angiopathy in elderly patients.

OBJECTIVE: The objective of this study was to evaluate the routine use of gradient-refocused echo MRI sequences in the detection of cortical cerebral microbleeding suggestive of cerebral amyloid angiopathy in elderly patients (> 70 years old). CONCLUSION: The addition of gradient-refocused echo sequences to routine brain MRI resulted in the identification of cerebral amyloid angiopathy-related microbleeding in 15.5% of elderly patients. In most (86.7%) of these patients with positive findings, cerebral amyloid angiopathy was not suspected clinically, and 46.7% of these patients were undergoing anticoagulant or aspirin therapy, placing them at an increased risk of recurrent intracranial hemorrhage and catastrophic stroke.

Frequent loss of imprinting of PEG1/MEST in invasive breast cancer.

The human PEG1 gene is a newly identified imprinted gene on 7q32. Genetic aberrations of this chromosomal region are often detected in invasive breast carcinomas. In this study, we show monoallelic PEG1 expression in normal breast tissue, indicating the presence of a functional imprint, and more importantly, we demonstrate loss of imprinting (LOI) in all of seven informative invasive breast carcinomas. In contrast to this, in one case of atypical ductal hyperplasia (ADH) found in residual breast, imprinting was maintained. This raises the possibility that aberrant imprinting of PEG1 may be involved in the progression from hyperplasia to invasive breast cancer.